Moraxella catarrhalis (Mc) causes up to 20% of otitis media cases in children and ~10% of respiratory infections in adults with chronic obstructive pulmonary disease (COPD). These infections are a matter of concern due to the current lack of a vaccine and the rapid emergence of antibiotic resistance in clinical isolates. Additionally, the high carriage rates in children, coupled with the effectiveness of the pneumococcal conjugate vaccine at reducing the incidence of otitis media caused by Streptococcus pneumoniae, suggest that Mc infections may become even more prevalent. Our long-term goals are to study the molecular basis for Mc adherence to host surfaces and to evaluate the potential of interfering with this process to reduce the risk of infection by the organism. This is a logical approach to preventing disease since adherence is necessary for colonization of the host. Moreover, bacterial adhesins are proven vaccine antigens. During the previous funding period, we identified and characterized 5 Mc adhesins (Hag, McaP, OMPCD, MhaB1 &MhaB2). We believe that these adhesins contribute to the ability of Mc to colonize and persist in the host and that a vaccine containing these molecules will reduce the risk of infection. New preliminary data also revealed that Mc specifically binds to the cilia of normal human bronchial epithelial cells (NHBEC) cultures mimicking the airway lumen in vivo. We believe that understanding Mc interactions with these NHBEC cultures will allow us to optimize the design of adhesin-based vaccines and will identify additional targets for developing anti-infective approaches against this organism. We propose 3 specific aims: AIM 1: Test the hypothesis that the adhesins McaP, Hag, OMPCD, MhaB1 and/or MhaB2 contribute to the ability of Mc to colonize and persist in the nasopharynx using a recently validated chinchilla model. AIM 2: Test the hypothesis that vaccines containing recombinant forms of these adhesins will interfere with the ability of Mc to colonize and persist in the nasopharynx of chinchillas. AIM 3: Test the hypothesis that the adhesins McaP, Hag, OMPCD, MhaB1 and/or MhaB2 contribute to the ability of Mc to bind to ciliated cells of the human respiratory tract and modulate host-pathogen interactions.